Thus, the increase http://www.selleckchem.com/products/ganetespib-sta-9090.html in MMP 9 seen in astrocytes was also not dependent on the species of origin of the albumin. None of the albumin prepara tions tested above induced a change in the level of MMP 2 produced by astrocytes. Fi nally, we examined whether the response to BSA was specific by comparing it with the response to another high molecular weight molecule. Cells treated with 0. 1 mmol/l dextran did not show any increase in the level of MMP 9 compared with control cells, and dextran did not induce any change in the level of MMP 2 produced by astrocytes. Albumin induced increase in matrix metalloproteinase 9 is suppressed by inhibition of p38 mitogen activated protein kinase and extracellular signal regulated protein kinase, but not c Jun N terminal kinase We have previously shown that activation of astrocytes induced by albumin involves activation of the MAPK pathways.

We confirmed this finding here by show ing that treatment of the astrocytes with albumin for 90 minutes induced an increase Inhibitors,Modulators,Libraries in the level of phosphory lated p38 MAPK, ERK and JNK. To determine whether the activation of MMP 9 pro duced by albumin was mediated by MAPKs, we pre treated astrocytes with either the p38 MAPK inhibitor SB203580, the ERK pathway inhibitor PD98059, or the JNK inhibitor SP600125. We then exposed the cells to albumin and measured MMP 9 activation after 24 hours of recovery. Inhibition of the Inhibitors,Modulators,Libraries p38 MAPK pathway significantly attenuated the increase in MMP 9 induced by albumin. Inhibition of the ERK pathway significantly attenuated the increase in MMP 9 induced by albumin, but only at the highest concentra tion of inhibitor used.

In contrast, the release of MMP 9 in response to albumin was not affected by inhibition of JNK. The level of MMP 2 mea sured in the conditioned media of astrocytes was not affected by the presence of the MAPK inhibitors. Albumin induced increase in matrix metalloproteinase 9 is mediated Inhibitors,Modulators,Libraries via NADPH oxidase and reactive oxygen species Treatment of astrocytes with albumin induced an in crease in the production of ROS as measured by in crease in carboxy H2DCF DA fluorescence compared Inhibitors,Modulators,Libraries with the control cells. Pre treatment of cells with a combination of the antioxidant enzymes PEG SOD and PEG CAT suppressed the DCF DA fluorescence caused by albumin, indicating that the fluorescent signal was due to an increase in ROS. Expos ure to the positive control, TBHP, confirmed Inhibitors,Modulators,Libraries that increased DCF DA fluorescence can be detected in astrocytes in the presence of oxidative stress. Treatment with PEG CAT alone, or in combination with PEG SOD, significantly selleck Ivacaftor suppressed the MMP 9 production induced by albumin. However, pre treatment with PEG SOD alone did not induce a significant change in the level of MMP 9 produced by astrocytes.